The purpose of this research study is to compare the survival rates of patients with better risk disease undergoing hematopoietic stem cell transplant (HSCT) to the survival rates reported in the medical literature of similar patients undergoing reduced intensity HSCT from matched related donors.

Overall Survival (OS) in patients with haploidentical family donors with hematological malignancies in morphological or radiographic remission or with chemosensitive, indolent diseases [ Time Frame: At 2 years ] [ Designated as safety issue: No ]

The primary null hypothesis is that 2 year OS rate is at most 35%. This hypothesis will be rejected if the 95% confidence interval for year OS rate computed from the estimated Kaplan-Meier survival curves will be entirely above 0.35.

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 60 minutes on days -11 to -8 and thiotepa IV over 2 hours on days -11 to -9. Patients undergo TBI on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.

TRANSPLANTATION: Patients undergo DLI on day -6 and CD-34+ allogeneic PBSCT on day 0.

GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID on days -1 to 28.

Drug: Fludarabine

Given IV

Other Names:

fludarabine phosphate

Fludara

Drug: Thiotepa

Given IV

Other Names:

N,N'N'-triethylenethiophosphoramide

ThioTEPA

Radiation: Total Body Irradiation (TBI)

2 Gy administered as part of the conditioning regimen

Other Name: radiotherapy

Biological: Donor Lymphocyte Infusion (DLI)

Undergo DLI

Other Name: buffy coat fusion

Drug: Cyclophosphamide (CY)

Given IV

Other Names:

Endoxan

Cytoxan

Neosar

Procytox

Revimmune

cytophosphane

Drug: Tacrolimus

Given IV or PO

Other Names:

FK-506

Fujimycin

Drug: Mycophenolate mofetil

Given IV

Other Names:

MMF

CellCept

Device: Allogeneic hematopoietic stem cell transplantation

Undergo CD34+ allogeneic PBSCT

Other Name: CliniMACS

Procedure: Peripheral blood stem cell transplantation (PBSCT)

Undergo CD34+ allogeneic PBSCT

Other Names:

PBPC transplantation

PBSC transplantation

peripheral blood progenitor cell transplantation

transplantation

peripheral blood stem cell

Detailed Description:

PRIMARY OBJECTIVES:

I. To compare the overall survival (OS) rate at 2 years post treatment using the Jefferson 2 step reduced intensity conditioning (RIC) approach in patients with haploidentical family donors with hematological malignancies in morphological or radiographic remission or with chemosensitive, indolent diseases to historical OS rates in similar populations after RIC matched donor HSCT as reported in the literature.

SECONDARY OBJECTIVES:

I. To compare the treatment-related mortality (TRM) rate at 2 years for patients treated on this study to the historical TRM rates of patients undergoing RIC matched-sibling HSCT as reported in the literature.

II. To compare the 2 year relapse rates and relapse related mortality of patients with myeloid diseases to that of patients with lymphoid diseases who are treated on this Thomas Jefferson University (TJU) RIC 2 step approach.

III. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treated on the TJU RIC 2 step approach.

V. To evaluate the incidence of TRM at 100 days in patients treated on the TJU RIC 2 step approach.

OUTLINE:

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -11 to -8 and thiotepa IV over 2 hours on days -11 to -9. Patients undergo total body irradiation (TBI) on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.

GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or orally (PO) with taper beginning on day 42. Patients also receive mycophenolate mofetil IV twice daily (BID) on days -1 to 28.

After completion of study treatment, patients are followed up periodically for 2 years.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Any patient with hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. Patients treated on this protocol will be without morphological evidence of disease (complete remission or "CR"), or if the patient has evidence of disease, the patient must have had at least a good partial response (PR) to the most recent therapy and the disease must be chemoresponsive.

Myeloma without morphological evidence of disease, or a deep PR to the most recent therapy

Myeloproliferative disorders with at least a PR to current therapy

Aplastic Anemia

A hematological or oncological disease (not listed) that meets the criteria reviewed above (in CR or with a good PR).

Patients must have a related donor who is HLA mismatched at 2, 3, or 4 antigens at the HLA-A; B; C; DR loci in the GVHD direction. (Patients with related donors who are HLA identical or are a 1-antigen mismatch may be treated on this therapeutic approach, but will have their outcomes will not be part of the statistical aims of the study (see Summary section).

Patients must adequate organ function:

LVEF (Left ventricular end diastolic function) of >50%

DLCO (Diffusing Capacity of the Lung for Carbon Monoxide ) ≥50% of predicted corrected for hemoglobin

Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder

Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit anti-thymocyte globulin and have an anti-thymocyte globulin level of > 2 ugm/ml

Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01384513